Although the observation that platelets play an important role in thrombosis and atherogenesis is well established, many important aspects of the interaction between platelets and the vessel wall remain unknown. We intend to explore features of this interaction to promote a clearer understanding of the pathophysiologic mechanisms involved in thrombosis and atherogenesis. Our underlying hypothesis is that platelet-secreted materials or other humoral materials released during hemostatic reactions to injury can lead to the proliferation of vascular smooth muscle cells and subsequent intimal thickening. In exploring this hypothesis, we will seek to study the in vivo effect of two platelet-secreted materials: platelet-derived growth factor and serotonin. To fully define the hemostatic influence on vessel wall biology, we will examine the role of serotonin antagonist in smooth muscle cell proliferation. Lastly, we will study the effect of minimal endothelial cell injury on the hemostatic response and intimal growth. These studies should clarify the role of platelet-secreted materials in vessel wall pathophysiology in vivo.